A Phase I/II Trial of AK117 (Anti-CD47) in Patients With Higher-risk Myelodysplastic Syndrome
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 136
- 试验地点
- 1
- 主要终点
- Rate of Complete Remission (CR)
研究概览
简要总结
This is a open label, phase I/II study. All patients are diagnosed with higher-risk MDS, Eastern Cooperative Oncology Group (ECOG) performance status 0-2. The purpose of this study is to evaluate the safety and efficacy of AK117 + azacitidine in subjects with higher-risk MDS.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years (at the time consent is obtained).
- •Be able and willing to provide written informed consent and to comply with all requirements of study participation (including all study procedures).
- •Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 -
- •Has a life expectancy of at least 12 weeks.
- •Phase 1: Diagnosis of higher-risk MDS that is either previously untreated or relapsed/refractory.
- •Phase 2: Diagnosis of higher-risk MDS that is previously untreated.
- •White blood cell count ≤ 25 x 10^9/L (hydroxyurea may be used to reduce the WBC count).
- •Has adequate organ function.
- •All female and male subjects of reproductive potential must agree to use an effective method of contraception, as determined by the Investigator, during and for 120 days after the last dose of study treatment.
排除标准
- •Is currently participating in a study of an investigational agent or using an investigational device.
- •Has undergone major surgery within 30 days of Study Day
- •Has a known additional malignancy that is progressing or requires systemic treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
- •Previous allogeneic hematopoietic stem cell transplant (allo-HSCT) .
- •Prior treatment with any anti-CD47 or anti-SIRPα (signal regulatory protein alpha) agent.
- •Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- •Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
- •History of myocardial infarction, unstable angina, congestive heart failure within 12 months prior to day 1 of study treatment.
- •Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of this subject to participate, in the opinion of the treating investigator.
- •Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
- •Has received a live virus vaccine within 30 days of the planned first dose of study therapy.
- •Is pregnant, breastfeeding, or expecting to conceive or father a child within the projected duration of the study including 120 days following the last dose of study treatment.
- •Has any concurrent medical condition that, in the opinion of the Investigator, would complicate or compromise compliance with the study or the well-being of the subject.
研究组 & 干预措施
AK117+ azacitidine
Phase 1: Subjects will receive escalating doses of A117 in combination with azacitidine 75 mg/m2 subcutaneous daily for 7 days of a 28 day cycle;
Phase 2: Subjects will receive AK117 at the recommended Phase 2 dose in combination with azacitidine 75 mg/m2 subcutaneous daily for 7 days of a 28-day cycle.
干预措施: AK117 (Drug)
AK117+ azacitidine
Phase 1: Subjects will receive escalating doses of A117 in combination with azacitidine 75 mg/m2 subcutaneous daily for 7 days of a 28 day cycle;
Phase 2: Subjects will receive AK117 at the recommended Phase 2 dose in combination with azacitidine 75 mg/m2 subcutaneous daily for 7 days of a 28-day cycle.
干预措施: Azacitidine (Drug)
结局指标
主要结局
Rate of Complete Remission (CR)
时间窗: Approximately 6 months
Number of participants achieving a CR per International Working Group (IWG) 2006 criteria.
Number of participants with adverse events (AEs)
时间窗: Up to approximately 2 years.
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Duration of Complete Remission (DoCR)
时间窗: Up to approximately 2 years.
The DoCR is measured from the time measurement criteria are first met for CR to the first date of relapse or death, whichever occurs earlier.
次要结局
- Objective Response Rate (ORR)(Up to approximately 2 years.)
- Progression Free Survival (PFS)(Up to approximately 2 years.)
- Duration of Response (DOR)(Up to approximately 2 years.)
- Maximum observed concentration (Cmax) of AK117(Up to 2 years.)
- Anti-drug antibodies (ADA)(Up to 2 years.)